Studies on the reactivity and selectivity of positively charged aromatic and polyaromatic σ-radicals in a Fourier-transform ion cyclotron resonance (FT -ICR) mass spectrometer

Linhong Jing, Purdue University

Abstract

Aromatic σ-radicals, formed in biological systems from healthcare agents and antitumor drugs, can abstract a H-atom from a sugar moiety of DNA or an amino acid residue of a protein, which leads to DNA or protein damage. However, the factors that control the reactivities and regioselectivities of aromatic σ-radicals in H-abstraction are still not well understood. The focus of this thesis was to explore these factors by using Fourier-transform ion cyclotron resonance mass spectrometry and the “distonic ion approach”. Hydrogen abstraction by phenyl radicals was found to be controlled by the calculated (B3LYP/6-31+G(d)) vertical ionization energy of the hydrogen donors (IE) and the vertical electron affinity of the phenyl radicals (EA). An exponential correlation between the H-abstraction efficiency and IE - EA was established by systematically investigating the reactions of twenty nine structurally different, charged phenyl radicals with eighteen different hydrogen donors, which included five model compounds of sugars, three sugars, four amino acids, and six other hydrogen donors. A novel experimental method was developed for obtaining quantitative selectivity information for H-abstraction by phenyl radicals from different sites of an unlabeled substrate. The selectivity of five phenyl radicals toward ethanol, eight radicals toward isopropanol, and six radicals toward L-alanine, was determined. The results show that αC-H is the most reactive site for all of the reactions studied. For ethanol and isopropanol, the selectivity of radicals toward αC-H decreases while that toward βC-H increases as the radical's vertical EA increases. For L-alanine, the preference for αC-H only slightly decreases with the radical's vertical EA, while a selectivity inversion occurs for the βC-H and N-H sites (selectivity for βC-H increases and that for N-H decreases).

Degree

Ph.D.

Advisors

Kenttamaa, Purdue University.

Subject Area

Analytical chemistry|Organic chemistry|Chemistry

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